The relation of the gonads to pituitary-adrenal function, primarily in rats, but also in hamster, guinea pigs and mice, is the general problem under investigation. Experimental manipulations include: gonadectomy, adrenalectomy, hypophysectomy, administration of gonadal, adrenal and pituitary hormones, and the application of various stresses. Evaluation of hypothalamic function as it pertains to regulation of ACTH secretion includes assessment of content of corticotropin-releasing- activity. Electrical activity of single neurons is recorded in intact and diencephalic island preparations. Pituitary-adrenal function is monitored simultaneously by measurements of plasma corticosterone using competitive protein binding (CPB). Pituitary secretion of ACTH is determined in vivo and in vitro by appropriate bioassay techniques. Steroid production by adrenal slices and homogenates in vitro is measured by acid fluorescence, ultra-violet absorption, and blue tetrazolium. Radioactive steroid substrates are also used with isolation and identification of products by thin-layer and paper chromatography. Of particular interest is adrenal 5 alpha-reductase and regulation of its activity by hormones, which include: estradiol, testosterone, ACTH, prolactin and STH. Both their simple and interactional effects will be evaluated. In follow-up to in vitro studies, adrenal secretions of reduced metabolites in vivo is under investigation using double label isotope dilution and CPB as well as chemical methods. The possibility that secretion of reduced steroid metabolites contributes to human adrenal dysfunction is also being explored. Plasma binding of corticosterone and the clearance and metabolism of steroids by the liver are also examined in relation to the effects of the gonadal hormones.